Clinical and molecular characterization of patients with acute myeloid leukemia and sole trisomies of chromosomes 4, 8, 11, 13 or 21
| Autor: | Clara D. Bloomfield, Bayard L. Powell, Andrew J. Carroll, Shelley Orwick, Ann-Kathrin Eisfeld, Jessica Kohlschmidt, Bhavana Bhatnagar, Dimitrios Papaioannou, Richard Stone, Deedra Nicolet, Krzysztof Mrózek, John C. Byrd, Jonathan E. Kolitz, Christopher J. Walker, James S. Blachly |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0301 basic medicine Cancer Research Spliceosome NPM1 Myeloid Chromosomes Human Pair 21 Trisomy Article 03 medical and health sciences 0302 clinical medicine Humans Medicine Gene Aged Aged 80 and over Chromosomes Human Pair 13 business.industry Chromosomes Human Pair 11 Chromosome Myeloid leukemia Hematology Middle Aged medicine.disease Molecular biology Leukemia Myeloid Acute Leukemia 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Female Chromosomes Human Pair 4 business Nucleophosmin Chromosomes Human Pair 8 |
| Zdroj: | Leukemia. 34:358-368 |
| ISSN: | 1476-5551 0887-6924 |
| Popis: | Sole trisomies of chromosomes 4, 8, 11, 13 and 21 account for 89–95% of all sole trisomies in adult AML patients. We analyzed clinical and molecular characteristics of 138 de novo AML patients with sole +4, +8, +11, +13 or +21, and compared them with AML patients with those trisomies occurring in addition to other chromosome abnormalities (non-sole trisomy) and with cytogenetically normal AML (CN-AML) patients. Mutations in methylation-related genes were most commonly observed within each sole trisomy group (+4, 55%; +8, 58%; +11, 71%; +13, 71%; +21, 75% of patients). Patients with sole trisomies, excluding +4, also had frequent mutations in spliceosome genes (+8, 43%; +11, 65%; +13, 65%; +21, 45% of patients). In contrast, +4 patients frequently had mutations in transcription factor genes (44%) and NPM1 (36%). While 48% of patients with sole trisomies harbored mutations in a spliceosome gene, spliceosome mutations were observed in only 24% of non-sole trisomy (n = 131, P < 0.001) and 19% of CN-AML patients (n = 716, P < 0.001). Our data suggest that mutations affecting methylation-related genes are a molecular hallmark of sole trisomies. Mutations in spliceosome genes were also commonly observed in many sole trisomy patients and represent a novel finding in this cytogenetic subgroup. |
| Databáze: | OpenAIRE |
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